Emerging investigator series: characterization of silver and silver nanoparticle interactions with zinc finger peptides
Emerging investigator series: characterization of silver and silver nanoparticle interactions with zinc finger peptides
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DOI：
10.1039/c9en00065h
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发表时间：
2019-08-01
影响因子：
7.3
通讯作者：
Wheeler, Korin E.
中科院分区：
文献类型：
--
作者：
Park, Grace;Amaris, Zoe N.;Wheeler, Korin E.
在生物系统中，工程银纳米材料（AgENM）的化学和物理转化部分由蛋白质和其他生物分子介导。金属蛋白与AgENMs的相互作用也是理解毒性，抗菌和耐药机制的核心。尽管锌指（ZF）肽易于获得硫醇盐和胺配体，但迄今为止锌指（ZF）肽在与AgENM及其Ag（i）氧化溶解产物的反应中没有研究。我们报告了光谱研究，表征AgENM和Ag（i）与两种ZF肽的相互作用，这两种ZF肽在序列上不同，但在金属结合配体上不同：ZF共有肽CP-CCHC和HIV-1核衣壳蛋白p7（NCp7_C）的C-末端锌指结构域。两种ZF肽均催化AgENM（10和40 nm，柠檬酸盐包被）溶解和团聚，这是影响生物活性的两种重要AgENM转化。AgENM及其氧化溶解产物Ag（i）（aq）也介导ZF肽结构和金属化的变化。Ag（i）到apo-ZF肽中的光谱滴定显示Ag（i）-硫醇盐电荷转移带，指示Ag（i）-ZF结合。Zn（ii）-NCp_7配合物的荧光研究表明，Ag（i）也有效地与Zn（ii）竞争以驱动Zn（ii）从ZF中置换。在与AgENMs相互作用后，Zn（ii）结合ZF肽在圆二色谱中显示出二级结构的变化，朝向apo样结构。结果表明，Ag（i）和AgENMs可以改变ZF蛋白在细胞内的功能。
In biological systems, chemical and physical transformations of engineered silver nanomaterials (AgENMs) are mediated, in part, by proteins and other biomolecules. Metalloprotein interactions with AgENMs are also central in understanding toxicity, antimicrobial, and resistance mechanisms. Despite their readily available thiolate and amine ligands, zinc finger (ZF) peptides have thus far escaped study in reaction with AgENMs and their Ag(i) oxidative dissolution product. We report spectroscopic studies that characterize AgENM and Ag(i) interactions with two ZF peptides that differ in sequence, but not in metal binding ligands: the ZF consensus peptide CP-CCHC and the C-terminal zinc finger domain of HIV-1 nucleocapsid protein p7 (NCp7_C). Both ZF peptides catalyze AgENM (10 and 40 nm, citrate coated) dissolution and agglomeration, two important AgENM transformations that impact bioreactivity. AgENMs and their oxidative dissolution product, Ag(i)(aq), mediate changes to ZF peptide structure and metalation as well. Spectroscopic titrations of Ag(i) into apo-ZF peptides show an Ag(i)-thiolate charge transfer band, indicative of Ag(i)-ZF binding. Fluorescence studies of the Zn(ii)-NCp_7 complex indicate that the Ag(i) also effectively competes with the Zn(ii) to drive Zn(ii) displacement from the ZFs. Upon interaction with AgENMs, Zn(ii) bound ZF peptides show a secondary structural change in circular dichroism spectroscopy toward an apo-like structure. The results suggest that Ag(i) and AgENMs may alter ZF protein function within the cell.